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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034604993  22 PIVVVLSGSMEPAFHRGDLLFLTNF--REDPIRAGEIVVFKVEGR-DIPIVHRVikvhekdngdIKFLTKGDN--NEVDD 96
Cdd:cd06530     1 EPVVVPGGSMEPTLQPGDLVLVNKLsyGFREPKRGDVVVFKSPGDpGKPIIKRV----------IGYFVLGDNrnNSLDS 70

                          90       100
                  ....*....|....*....|
gi 1034604993  97 RGLYKegqnwLEKKDVVGRA 116
Cdd:cd06530    71 RYWGP-----VPEDDIVGKV 85

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

                          10        20        30        40
                  ....*....|....*....|....*....|....*....|....*....
gi 1034604993  28 SGSMEPAFHRGDLLFLT--NFREDPIRAGEIVVFKV-EGRDIPIVHRVI 73
Cdd:COG0681    40 SGSMEPTLLVGDRLLVNklSYGFGEPKRGDIVVFKYpEDPSKDYIKRVI 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        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034604993  22 PIVVVLSGSMEPAFHRGDLLFLTNF--REDPIRAGEIVVFKVEGR-DIPIVHRVikvhekdngdIKFLTKGDN--NEVDD 96
Cdd:cd06530     1 EPVVVPGGSMEPTLQPGDLVLVNKLsyGFREPKRGDVVVFKSPGDpGKPIIKRV----------IGYFVLGDNrnNSLDS 70

                          90       100
                  ....*....|....*....|
gi 1034604993  97 RGLYKegqnwLEKKDVVGRA 116
Cdd:cd06530    71 RYWGP-----VPEDDIVGKV 85

Peptidase S24-like;

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1034604993  15 VLTGSESPIVVVLSGSMEPAFHRGDLLFLTnfREDPIRAGEIVVFKVEGrdIPIVHRVIkvheKDNGDIKFLTkgDNNEV 94
Cdd:pfam00717  29 LSPPGNLFALRVKGDSMEPGIPDGDLVLVD--PSREARNGDIVVARLDG--EATVKRLY----RDGGGIRLIS--LNPEY 98

                  ...
gi 1034604993  95 DDR 97
Cdd:pfam00717  99 PPI 101

Peptidase S24 LexA-like proteins are involved in the SOS response leading to the repair of single-stranded DNA within the bacterial cell. This family includes: 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 LexA-like proteins contain two-domains: an N-terminal DNA binding domain and a C-terminal domain (CTD) that provides LexA dimerization as well as cleavage activity. They undergo autolysis, cleaving at an Ala-Gly or a Cys-Gly bond, separating the DNA-binding domain from the rest of the protein. In the presence of single-stranded DNA, the LexA, UmuD and MucA proteins interact with RecA, activating self cleavage, thus either derepressing transcription in the case of LexA or activating the lesion-bypass polymerase in the case of UmuD and MucA. The LexA proteins are 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. LexA sequence homologs are found in almost all of the bacterial genomes sequenced to date, covering a large number of phyla, suggesting both, an ancient origin and a widespread distribution of lexA and the SOS response.

                          10        20        30
                  ....*....|....*....|....*....|....*
gi 1034604993  30 SMEPAFHRGDLLFLTnfREDPIRAGEIVVFKVEGR 64
Cdd:cd06529     9 SMEPTIPDGDLVLVD--PSDTPRDGDIVVARLDGE 41