Conserved Protein Domain Family

cd07014: S49_SppA 
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Signal peptide peptidase A
Signal peptide peptidase A (SppA; Peptidase S49; Protease IV): SppA is an intramembrane enzyme found in all three domains of life and is involved in the cleavage of signal peptides after their removal from the precursor proteins by signal peptidases. Unlike the eukaryotic functional homologs that are proposed to be aspartic proteases, site-directed mutagenesis and sequence analysis have shown these bacterial, archaeal and thylakoid SppAs to be ClpP-like serine proteases. The predicted active site serine for members in this family occurs in a transmembrane domain, cleaving peptide bonds in the plane of the lipid bilayer. Mutagenesis studies also suggest that the catalytic center comprises a Ser-Lys dyad (both residues absolutely conserved within bacteria, chloroplast and mitochondrial signal peptidase family members) and not the usual Ser-His-Asp catalytic triad found in the majority of serine proteases. In addition to the carboxyl-terminal protease domain that is conserved in all the S49 family members, the E. coli SppA contains an amino-terminal domain (sometimes referred to as 67K type). Others, including sohB peptidase, protein C, protein 1510-N and archaeal signal peptide peptidase, do not contain the amino-terminal domain (sometimes referred to as 36K type). Interestingly, the single membrane spanning E. coli SppA carries out catalysis using a Ser-Lys dyad with the serine located in the conserved carboxy-terminal protease domain and the lysine in the non-conserved amino-terminal domain. This family also contains homologs that either have been found experimentally to be without peptidase activity, or lack amino acid residues that are believed to be essential for the catalytic activity of peptidases.
PSSM-Id: 132925
View PSSM: cd07014
Aligned: 4 rows
Threshold Bit Score: 188.597
Threshold Setting Gi: 163311059
Created: 21-Nov-2008
Updated: 2-Oct-2020
Aligned Rows:
Conserved site include 1 residue -Click on image for an interactive view with Cn3D
Feature 1:active site residues [active site]
  • Comment:The N- and C-terminal halves of SppA in E. coli are tandem repeats and the Ser/Lys dyad is arranged such that the nucleophile Ser is located in the C-terminal half whereas the general base Lys is located in the N-terminal half.
  • Structure:3BEZ: Escherichia coli Signal peptide peptidase A (SppA)
    View structure with Cn3D

Sequence Alignment
Format: Row Display: Color Bits: Type Selection:
Feature 1                                                                                     
3BEZ_A    305 VVFANGaixdgee------------------tqgnvgGDTTAAQIRDARLdpkvkAIVLRVNSpgg-svTASEVIRAELA 365 Escherichia coli
3BF0_A    305 VVFANGaimdgee------------------tqgnvgGDTTAAQIRDARLdpkvkAIVLRVNSpgg-svTASEVIRAELA 365 Escherichia coli
3BEZ_A     35 LLDISGvivdkpdssqrfsklsrqllgassdrlqensLFDIVNTIRQAKDdrnitGIVXDLKNfaggdqPSXQYIGKALK 114 Escherichia coli
ABX56715   60 IIHVNGvisryanlf--------------havcggvsTEVLAKEFNAALNessvkAVILNVDSpgg-eaSGIHELSEMIH 124 Vibrio shilonii
Feature 1                       #                                                             
3BEZ_A    366 AaraagKPVVVSXggXAASGGYWISTPanyIVANPSTLTGsiGIFGVittvensldsigvhtdgv---stspladvsitr 442 Escherichia coli
3BF0_A    366 AaraagKPVVVSMggMAASGGYWISTPanyIVANPSTLTGsiGIFGVittvensldsigvhtdgv---stspladvsitr 442 Escherichia coli
3BEZ_A    115 EfrdsgKPVYAVGe-NYSQGQYYLASFankIWLSPQGVVDlhGFATNglyykslldklkvsthvfrvgtyksavepfird 193 Escherichia coli
ABX56715  125 Asr-gkKPVRAYVggDGCSAAYWITTAcdrVTMDATARVGsiGTVVSfvkrpdaegakrfefv-------ssqspnkrld 196 Vibrio shilonii
Feature 1                                                                                   
3BEZ_A    443 alppeaQLXXQLSIENGYKRFITLVADarhstpe--------qidkiaqGHVWTGQDAKANGLVDSLgdfdDAVAKAA 512 Escherichia coli
3BF0_A    443 alppeaQLMMQLSIENGYKRFITLVADarhstpe--------qidkiaqGHVWTGQDAKANGLVDSLgdfdDAVAKAA 512 Escherichia coli
3BEZ_A    194 dxspaaREADSRWIGELWQNYLNTVAAnrqipaeqvfpgaqgllegltkTGGDTAKYALENKLVDALassaEIEKALT 271 Escherichia coli
ABX56715  197 peseqgQTAIQTQLDAMAEVFISRVARnmgvtsdk-------vksdfgqGGVKIGQQAVDAGMAHELgsleALIASLS 267 Vibrio shilonii

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