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 1491180748  36 PFMVVVSRSMEPTIRVNDLIIITKASPD--DIRVGDIIVFRSPLNPDMYIVHRVIQVIrsndriyfkTKGDN--NKYPDR 111
Cdd:cd06530     1 EPVVVPGGSMEPTLQPGDLVLVNKLSYGfrEPKRGDVVVFKSPGDPGKPIIKRVIGYF---------VLGDNrnNSLDSR 71

                          90
                  ....*....|....
gi 1491180748 112 W--VVDQDNLIGRV 123
Cdd:cd06530    72 YwgPVPEDDIVGKV 85

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

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1491180748   9 ILYTVITLILLYLAISFGIEyvfgvdkPFmVVVSRSMEPTIRVNDLIIITKAS--PDDIRVGDIIVFRSPLNPDMYIVHR 86
Cdd:COG0681    15 LKSIVIALLLALLIRTFVFE-------PF-VIPSGSMEPTLLVGDRLLVNKLSygFGEPKRGDIVVFKYPEDPSKDYIKR 86

                  ..
gi 1491180748  87 VI 88
Cdd:COG0681    87 VI 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 1491180748  36 PFMVVVSRSMEPTIRVNDLIIITKASPD--DIRVGDIIVFRSPLNPDMYIVHRVIQVIrsndriyfkTKGDN--NKYPDR 111
Cdd:cd06530     1 EPVVVPGGSMEPTLQPGDLVLVNKLSYGfrEPKRGDVVVFKSPGDPGKPIIKRVIGYF---------VLGDNrnNSLDSR 71

                          90
                  ....*....|....
gi 1491180748 112 W--VVDQDNLIGRV 123
Cdd:cd06530    72 YwgPVPEDDIVGKV 85

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 1491180748   7 LRILYTVITLILLYLAISFgieYVFGvdkPFmVVVSRSMEPTIRVNDLIIITKAS--PDDIRVGDIIVFRSPLNPDMYIV 84
Cdd:pfam10502   2 LEWVKAIVIALLLALLIRT---FLFE---PY-VVPGGSMSPTLPIGDYLIVNKFSygLGEPKRGDIVVFRPPEGPGVPLI 74

                          90
                  ....*....|....*....
gi 1491180748  85 HRVI-----QVIRSNDRIY 98
Cdd:pfam10502  75 KRVIglpgdRVEYKDDQLY 93

signal peptidase I, bacterial type; This model represents signal peptidase I from most bacteria. Eukaryotic sequences are likely organellar. Several bacteria have multiple paralogs, but these represent isozymes of signal peptidase I. Virtually all known bacteria may be presumed to A related model finds a simlar protein in many archaea and a few bacteria, as well as a microsomal (endoplasmic reticulum) protein in eukaryotes. [Protein fate, Protein and peptide secretion and trafficking]

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1491180748  37 FMVVVSRSMEPTIRVNDLIIITKASP--DDIRVGDIIVFRSPLNPDMYIVHRVI-----QVIRSNDRIYfktkgDNNKYP 109
Cdd:TIGR02227   5 PYKIPGGSMEPTLKEGDRILVNKFAYrtSDPKRGDIVVFKDPDTNKNIYVKRIIglpgdKVEFRDGKLY-----INGKKI 79

                  .
gi 1491180748 110 D 110
Cdd:TIGR02227  80 D 80

Phage repressor protein C, contains Cro/C1-type HTH and peptisase s24 domains [Mobilome: prophages, transposons];

                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1491180748  44 SMEPTIRVNDLIIItKASPDDIRVGDIIVFRSplnPDMYIVHRVIQviRSNDRIYFKTkgDNNKYPDrWVVDQDNL---- 119
Cdd:COG2932    44 SMEPTIRDGDIVLV-DPSDTEIRDGGIYVVRT---DGELLVKRLQR--RPDGKLRLIS--DNPAYPP-IEIPPEDAdeie 114

                  ....*.
gi 1491180748 120 -IGRVL 124
Cdd:COG2932   115 iIGRVV 120

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        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1491180748  37 FMVVVSRSMEPTIRVNDLIIITKAspDDIRVGDIIVFRsplNPDMYIVHRViqVIRSNDRIYFKTkgDNNKYPDrWVVDQ 116
Cdd:cd06529     2 ALRVKGDSMEPTIPDGDLVLVDPS--DTPRDGDIVVAR---LDGELTVKRL--QRRGGGRLRLIS--DNPAYPP-IEIDE 71

                  ....*....
gi 1491180748 117 DNL--IGRV 123
Cdd:cd06529    72 EELeiVGVV 80