Family S49

Family

Summary Holotypes Alignment Tree Genomes Structure Literature

S49A

Summary Holotypes Alignment Tree Genomes Literature

S49B

Summary Holotypes Alignment Tree Genomes Literature

S49C

Summary Holotypes Alignment Tree Genomes Literature

Summary for family S49

NamePeptidase family S49 (protease IV family)
Family type peptidaseS49.001 - signal peptide peptidase A (Escherichia coli), MEROPS Accession MER0001299 (peptidase unit: 46-618)
Content of familyPeptidase family S49 contains endopeptidases.
History Identifier created: MEROPS 5.00 (20 April 2000)
Signal peptide peptidase A (SppA, S49.001, originally named protease IV) was probably discovered by Pacaud in E. coli (Pacaud, 1982; Pacaud, 1982), although the size of 34 kDa reported by Pacaud is only about half that currently accepted. Signal peptide peptidase A is so termed because it can degrade the released signal peptide of a lipoprotein. There are unrelated functional signal peptide peptidases including oligopeptidase A (M03.004) in bacteria and impas 1 endopeptidase (A22.003) in eukaryotes. There is also an unrelated "protease IV" in Pseudomonas aeruginosa (S01.281).
Many of the prokaryotic homologues are annotated as similar to the NfeD protein in the sequence databases. However, this is an error, because the original NfeD protein was a cyclodeaminase that shows no homology to the proteins in family S49 (Green et al., 2004). Green et al propose that these proteins instead be termed STOPP proteins, for Stomatin Operon Partner Protein.
Catalytic typeSerine
Active siteFrom the tertiary structure of SppA from Escherichia coli a catalytic triad has been proposed consisting of Lys209, Ser409 and Ser432 in which Lys209 is the general base, the hydroxyl group of Ser409 is the nucleophile and Ser432 orientates the lysine (Kim et al., 2009). The active site Lys is in the N-terminal domain and the active site serines in the C-terminal domain. In protein C from bacteriophage lambda (S49.003), which consists of only one domain, the active site residues are in the order Ser166, Ser188 and Lys218 (Medina et al., 2010).
Activities and specificitiesSppA is most active at pH 7.2 - 7.6. It hydrolyzes the N-blocked p-nitrophenyl esters of Gly, Ala, Phe, Val, Leu and (more slowly) Trp; Z-Val-NHPhNO2 has been used as an assay substrate (Pacaud, 1982; Ichihara et al., 1984). SppA does not hydrolyze casein, but is reported to hydrolyze some of the proteins present in a detergent extract of bacterial membranes (Pacaud, 1982; Palmer & St. John, 1987). Analysis of the peptide products of the SppA-catalyzed hydrolysis of the 20-amino acid lipoprotein signal peptide suggests that it does not require a free N- or C-terminus. It prefers hydrophobic amino acids on either side of the scissile bond and will not cleave a peptide containing fewer than six amino acids.
InhibitorsSppA from E. coli is inhibited by DFP, PMSF, antipain, leupeptin, chymostatin and elastatinal, but not by p-aminobenzamidine, EDTA, pCMB, iodoacetate, TLCK or 2-mercaptoethanol (Pacaud, 1982; Ichihara et al., 1984).
Molecular structureThe tertiary structure of SppA from Escherichia coli has been determined (Kim et al., 2009). The structure shows that the N- and C-terminal domains are structurally related probably derived from an ancestral gene duplication and fusion event. The structure is similar to that of endopeptidase clp from family S14, the active site residues can be superimposed and both families are included in the same clan, SK. Unlike endopeptidase clp, the proteins of family S49 contain multiple membrane-spanning domains (Green et al., 2004). In work with recombinant SppA from E. coli it was shown that the 67-kDa monomers could associate into tetramers in solution. Protein C from bacteriophage lambda consists of a single domain (Medina et al., 2010).
ClanSK
Basis of clan assignmentPredicted active site serine for members of this family and family S14 occur in the same order in the sequence: S, R/H, D.
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi details  
Plants details  
Animals details  
Viruses details  
Biological functionsSppA contributes to the destruction of cleaved signal pepides in the periplasmic space of E. coli acting in conjunction with oligopeptidase A, and it probably has a similar function in other bacteria (Ichihara et al., 1984; Novak, P. & Dev, I. K. 1988).
The inclusion of peptidases from family S49 in an operon with stomatin has led Green et al., (2004) to suggest that these STOPP proteins regulate the functions of the stomatins by cleaving them. Protein C of bacteriphage lambda (S49.003) is included in one of the two major groups of prohead maturation proteases in double-stranded-DNA bacteriophages (Liu & Mushegian, 2004).
Statistics for family S49Sequences:8694
Identifiers:9
Identifiers with PDB entries:3
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Subfamily S49A
Name Peptidase subfamily S49A
Subfamily type peptidase S49.001 - signal peptide peptidase A (Escherichia coli), MEROPS Accession MER0001299 (peptidase unit: 46-618)
Active site residues K209 S409 S431 
Statistics Sequences: 2211
Identifiers: 1
Identifiers with PDB entries: 1
Other databases INTERPRO IPR002142
PANTHER PTHR33209
PFAM PF01343
PFAM PF01972
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
signal peptide peptidase AS49.001Yes
subfamily S49A unassigned non-peptidase homologuesnon-peptidase homologue-
subfamily S49A unassigned peptidasesunassigned-
Subfamily S49B
Name Peptidase subfamily S49B
Subfamily type peptidase S49.003 - protein C (bacteriophage lambda) (bacteriophage lambda), MEROPS Accession MER0001303 (peptidase unit: 114-307)
Active site residues S166 S188 K218 
Statistics Sequences: 5015
Identifiers: 6
Identifiers with PDB entries: 0
Other databases INTERPRO IPR002142
PANTHER PTHR33209
PFAM PF01343
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
sohB peptidaseS49.002-
protein C (bacteriophage lambda)S49.003-
signal peptide peptidase A (Arabidopsis-type)S49.004-
archaean signal peptide peptidase 2S49.006-
Tpv SppA peptidaseS49.007-
BSn5_05605 g.p. (Bacillus subtilis)S49.A08-
subfamily S49B non-peptidase homologuesnon-peptidase homologue-
subfamily S49B unassigned peptidasesunassigned-
Subfamily S49C
Name Peptidase subfamily S49C
Subfamily type peptidase S49.005 - archaean signal peptide peptidase 1 (Pyrococcus horikoshii), MEROPS Accession MER0042954 (peptidase unit: 45-206)
Active site residues S97 K116 
Statistics Sequences: 1387
Identifiers: 1
Identifiers with PDB entries: 1
Other databases PFAM PF01343
PFAM PF01972
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
archaean signal peptide peptidase 1S49.005Yes
subfamily S49C non-peptidase homologuesnon-peptidase homologue-
subfamily S49C unassigned peptidasesunassigned-
Peptidases not assigned to subfamily
Peptidases and Homologues MEROPS ID Structure
signal peptide peptidase (Bacillus-type)S49.008Yes
family S49 non-peptidase homologuesnon-peptidase homologue-
family S49 unassigned peptidasesunassigned-