Family S6

Family

Summary Holotypes Alignment Tree Genomes Structure Literature

Summary for family S6

Family type peptidaseS06.001 - IgA1-specific serine peptidase (Neisseria-type) (Neisseria gonorrhoeae), MEROPS Accession MER0000278 (peptidase unit: 28-823)
Content of familyPeptidase family S6 contains serine endopeptidases of bacteria.
History Identifier created: Biochem.J. 290:205-218 (1993)
Family S6 contains IgA1-specific endopeptidase (S06.001) from Neisseria and Haemophilus, the serine protease autotransporters of enterobacteriacea (SPATE) produced by Escherichia coli and Shigella spp. and the Hap gene product of Haemophilus influenzae.
Catalytic typeSerine
Active site residuesH101 D151 S278 
Active siteThe catalytic residues of family S6 are His, Asp, Ser, occurring in that order. The active site Ser occurs in a Gly-Xaa-Ser-Gly-Xaa-Pro motif that is well conserved throughout families S1, S2, S7, S29 and S30. Because of this motif, S6 is a member of clan PA. The His and Asp residues are located approximately 190 and 120 residues toward the N-terminal from the catalytic Ser as demonstrated experimentally in the Hap protein from H. influenzae (Fink et al., 2001).
Activities and specificitiesBacterial IgA1 proteases cleave human IgA1 in a part of the hinge region that is absent from IgA2 (Poulsen & Kilian, 2004). They are highly specific prolyl endopeptidases, with the site of cleavage within the hinge region of human IgA1 differing between bacterial strains. Unlike the IgA peptidases the SPATE peptidases have not been shown to cleave IgA1. All SPATE proteins are highly immunogenic and each SPATE member is among the most predominant secreted proteins of their respective pathogens.
InhibitorsIgA1 peptidases are inhibited by peptide boronic acids (Bachovchin% etal, 1990). The Pet endopeptidase (one of the SPATE proteins) is inhibited by phenylmethylsulfonyl fluoride (PMSF). Inhibitors of Hap proteolysis include PMSF and secretory leukocyte protease inhibitor (LI17-001), a natural component of human respiratory tract secretions (Hendrixson & St Geme, 1998).
Molecular structureMembers of family S6 all display three distinct regions: an N-terminal signal sequence, an internal passenger domain and a C-terminal domain (beta domain) which forms a beta-barrel pore through which the protein is secreted. The C-terminal domain is autolytically removed upon activation. It is mosaic in nature, containing regions related to a variety of other proteins, including E. coli initiating factor 2 and rat plectin.
ClanPA
SubclanPA(S)
Basis of clan assignmentPredicted active site residues for members of this family and family S1 occur in the same order in the sequence: H, D, S.
Distribution of family Bacteria details  
Archaea -  
Protozoa -  
Fungi -  
Plants -  
Animals -  
Viruses details  
Biological functionsThe IgA1 serine peptidase, through the cleavage of the human IgA1 may interfere with the protecive functions of the principal mediator of specific immunity on mucosal surfaces. Cleavage of lysosomal-associated membrane protein-1 (LAMP1) and tumour necrosis factor-alpha receptor II may also contribute to pathogenesis. It has been suggested that human coagulation factor V cleavage by EspP (S06.002) could contribute to the mucosal haemorrhage observed in patients with haemorrhagic colitis (Brunder et al., 1997).
Pharmaceutical and biotech relevancePossible applications of the SPATE proteins include the expression of antigenic determinants for vaccine development, peptide libraries for epitope mapping or antibody specificity testing, and receptors or ligands for binding assays or simple purification. IgA1 proteases have potential applications for in vitro processing of recombinant proteins due to their sequence specificity (Pohlner et al., 1992).
Statistics for family S6Sequences:297
Identifiers:11
Identifiers with PDB entries:4
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Peptidases and Homologues MEROPS ID Structure
IgA1-specific serine peptidase (Neisseria-type)S06.001-
EspP peptidase (Escherichia coli)S06.002Yes
Tsh peptidaseS06.003Yes
Sat peptidaseS06.004Yes
Pic peptidaseS06.005-
Hap serine peptidaseS06.006Yes
IgA1-specific serine peptidase type 1 (Haemophilus sp.)S06.007-
IgA1-specific serine peptidase type 2 (Haemophilus sp.)S06.008-
EatA peptidase Mername-AA278 (Escherichia coli)S06.009-
EspC peptidaseS06.010-
SepA peptidaseS06.013-
family S6 non-peptidase homologuesnon-peptidase homologue-
family S6 unassigned peptidasesunassigned-