Family S9

Family

Summary Holotypes Alignment Tree Genomes Structure Literature H-seq M-seq

S9A

Summary Holotypes Alignment Tree Genomes Literature

S9B

Summary Holotypes Alignment Tree Genomes Literature

S9C

Summary Holotypes Alignment Tree Genomes Literature

S9D

Summary Holotypes Alignment Tree Genomes Literature

Summary for family S9

NamePeptidase family S9 (prolyl oligopeptidase family)
Family type peptidaseS09.001 - prolyl oligopeptidase (Sus scrofa), MEROPS Accession MER0000392 (peptidase unit: 428-710)
Content of familyPeptidase family S9 contains a varied set of serine-dependent peptidases.
History Identifier created: Biochem.J. 290:205-218 (1993)
Family S9 was first assembled by Rawlings et al., 1991, when it was realised that the newly determined prolyl oligopeptidase (S09.001) protein sequence was homologous to those of dipeptidyl-peptidase IV (DPP-IV; S09.003) and acylaminoacyl-peptidase (S09.004). Each of these is the type-example for a subfamily (S9A, S9B and S9C, respectively). Recently, a fourth subfamily (S9D) has been added to the family, containing glutamyl endopeptidase (S09.021).
Catalytic typeSerine
Active siteThe active site residues are in the order Ser, Asp, His in the sequence. The motifs around the active site Ser are characteristic for each subfamily: GGSXGGLL, where X is typically Asn or Ala (S9A), GWSYGGY (S9B), GGSYGG (S9C) and GGHSYGAFMT (S9D).
Activities and specificitiesMost members of the family show restricted specificities and are active mainly on oligopeptides, consistent with the steric hindrance of the catalytic site by the beta-propeller domain at the N-terminus (Fulop et al., 1998). An exception is the reported activity of fibroblast activation protein alpha (as seprase) on gelatin (Kelly, 1999). Although many peptidases in the family cleave prolyl bond, there are exceptions, such as oligopeptidase B (S09.010) which cleaves Arg and Lys bonds; acylaminoacyl-peptidase which is an omega-peptidase releasing an N-acylated amino acid from an oligopeptide blocked by a acetyl, chloroacetyl, formyl or carbamyl group (Jones et al., 1986); and glutamyl endopeptidase cleaves the synthetic substrate Z-Leu-Leu-Glu-naphthylamide (Yamauchi et al., 2001). Prolyl oligopeptidase is thiol-dependent.
InhibitorsMembers of the family are sensitive to DFP, like most serine peptidases. DPP-IV is poorly inhibited by PMSF (Kenny et al., 1976). There are no known naturally-occuring protein inhibitors.
Molecular structureTertiary structures have been solved for prolyl oligopeptidase (S09.001) and DPP-IV (S09.003). Each structure shows a multi-domain protein, with an N-terminal eight-bladed beta-propeller and a C-terminal peptidase unit. The structure of the peptidase unit is an alpha/beta/alpha sandwich and is similar to the fold of acetylcholinesterase, carboxylesterase, lipase, serine carboxypeptidases of family S10 (S10), prolyl aminopeptidase (S33.001), and many other enzymes. This fold has been described as 'alpha/beta-hydrolase' because most proteins with this fold are hydrolytic enzymes. Prolyl oligopeptidase (S09.001) and oligopeptidase B (S09.010) are monomers both in solution and in crystal structure, whereas dipeptidyl peptidase IV (S09.003) is a dimer, and mammalian acylaminoacyl-peptidase (S09.004) is a homotetramer (Kiss et al., 2004).
ClanSC
Basis of clan assignmentProtein fold of the peptidase unit for members of this family resembles that of serine carboxypeptidase D, the type example of clan SC.
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi details  
Plants details  
Animals details  
Viruses details  
Biological functionsMany peptidases in the family are believed to be important for the degradation of biologically active peptides: for example, DPP-IV metabolizes the insulinotropic hormone, glucagon-like peptide 1 (Holst & Deacon, 1998; Deacon & Holst, 2002). Members of the family are found in different cellular locations: prolyl oligopeptidase in intracellular, DDP-IV and fibroblast activation protein α (S09.007) are expressed on cell surfaces; and oligopeptidase B is secreted to the bacterial periplasm (Tsuru, 1998).
Statistics for family S9Sequences:47586
Identifiers:205
Identifiers with PDB entries:34
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Subfamily S9A
Name Peptidase subfamily S9A
Subfamily type peptidase S09.001 - prolyl oligopeptidase (Sus scrofa), MEROPS Accession MER0000392 (peptidase unit: 428-710)
Active site residues S554 D641 H680 
Statistics Sequences: 8426
Identifiers: 13
Identifiers with PDB entries: 3
Other databases CATH 3.40.50.1820
HOMSTRAD Peptidase_S9
HSSP 1o6g
INTERPRO IPR002471
PANTHER PTHR11757
PFAM PF00326
SCOP 53496
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
prolyl oligopeptidaseS09.001Yes
prolyl oligopeptidase homologue (Pyrococcus-type)S09.002-
oligopeptidase BS09.010-
PREPL A proteinS09.015-
prolyl oigopeptidase (zoomastigote)S09.033-
oligopeptidase B (zoomastigote)S09.034-
prolyl oligopeptidase (Myxococcus xanthus)S09.076Yes
At1g20380 (Arabidopsis thaliana)S09.A01-
At1g76140 (Arabidopsis thaliana)-type peptidaseS09.A02-
CG2528 protein (Drosophila melanogaster)S09.A73-
DDB_G0292866 g.p. (Dictyostelium discoideum)S09.A92-
DDB_G0274387 g.p. (Dictyostelium discoideum)S09.B02-
At1g69020 g.p. (Arabidopsis thaliana)S09.B08-
subfamily S9A non-peptidase homologuesnon-peptidase homologue-
subfamily S9A unassigned peptidasesunassignedYes
Subfamily S9B
Name Peptidase subfamily S9B
Subfamily type peptidase S09.003 - dipeptidyl-peptidase IV (eukaryote) (Homo sapiens), MEROPS Accession MER0000401 (peptidase unit: 503-766)
Active site residues S630 D708 H740 
Statistics Sequences: 8841
Identifiers: 23
Identifiers with PDB entries: 5
Other databases CATH 3.40.50.1820
HOMSTRAD Peptidase_S9
HSSP 1n1m
INTERPRO IPR001375
PANTHER PTHR11731
PFAM PF00326
PFAM PF00756
PFAM PF12695
PFAM PF12697
SCOP 82497
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
dipeptidyl-peptidase IV (eukaryote)S09.003Yes
dipeptidyl aminopeptidase AS09.005-
dipeptidyl aminopeptidase B (fungus)S09.006Yes
fibroblast activation protein alpha subunitS09.007Yes
dipeptidyl peptidase 4 (Aspergillus-type)S09.008-
dipeptidyl-peptidase 4 (bacteria-type 1)S09.009Yes
dipeptidyl-peptidase 4 (bacteria-type 2)S09.013-
DPF-3 peptidaseS09.016-
prolyl tripeptidyl peptidaseS09.017Yes
dipeptidyl-peptidase 8S09.018-
dipeptidyl-peptidase 9S09.019-
omega peptidase (Drosophila melanogaster)S09.069-
Xaa-Pro dipeptidylpeptidaseS09.073-
At5g24260 (Arabidopsis thaliana)S09.A03-
FrmB protein (Escherichi coli)S09.A38-
F14F18_80 protein (Arabidopsis thaliana)S09.A58-
CG11034 protein (Drosophila melanogaster)S09.A64-
CG11319 (Drosophila melanogaster)S09.A65-
dpf-2 g.p. (Caenorhabditis elegans)S09.A74-
K02F2.1 protein (Caenorhabditis elegans)S09.A75-
dpf-1 g.p. (Caenorhabditis elegans)S09.A76-
dipeptidyl aminopeptidase C14C4.15c (Schizosaccharomyces pombe)S09.A93-
bem46 g.p. (Schizosaccharomyces pombe)S09.A94-
subfamily S9B non-peptidase homologuesnon-peptidase homologue-
subfamily S9B unassigned peptidasesunassigned-
Subfamily S9C
Name Peptidase subfamily S9C
Subfamily type peptidase S09.004 - acylaminoacyl-peptidase (Homo sapiens), MEROPS Accession MER0000408 (peptidase unit: 477-728)
Active site residues S587 D675 H707 
Statistics Sequences: 7953
Identifiers: 54
Identifiers with PDB entries: 8
Other databases INTERPRO IPR001375
PANTHER PTHR11731
PFAM PF00135
PFAM PF00326
PFAM PF00756
PFAM PF01738
PFAM PF02230
PFAM PF05728
PFAM PF07859
PFAM PF12695
PFAM PF12697
PFAM PF12715
PFAM PF12740
SCOP 53474
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
acylaminoacyl-peptidaseS09.004-
dipeptidyl-peptidase 5S09.012-
sphingopyxin I lasso peptide isopeptidaseS09.032-
FLJ1 putative peptidaseS09.051-
Mername-AA194 putative peptidaseS09.052-
Mername-AA195 putative peptidaseS09.053-
Mername-AA196 putative peptidaseS09.054-
Mername-AA197 putative peptidaseS09.055-
dipeptidyl-peptidase IV, membrane-type (protistan)S09.056-
apsC g.p. (Aspergillus niger N400)S09.057-
C14orf29 proteinS09.061-
acylaminoacyl peptidase (Aeropyrum-type)S09.070Yes
trilobed proteaseS09.071Yes
tyrosyl aminopeptidase (Raphanus-type)S09.074-
dipeptidyl-peptidase 5 (Porphyromonas sp.)S09.075-
BSU33620 g.p. (Bacillus subtilis) and similarS09.946Yes
brefeldin A esteraseS09.951Yes
1700122C07Rik protein (Mus musculus)S09.963-
protein 9430007A20RIK (Mus musculus)S09.968-
carboxylesterase-related proteinS09.986-
At4g24760 (Arabidopsis thaliana)S09.A04-
At3g48690 (Arabidopsis thaliana)S09.A09-
At5g23530 (Arabidopsis thaliana)S09.A10Yes
At5g16080 (Arabidopsis thaliana)S09.A12-
At3g48700 (Arabidopsis thaliana)S09.A13-
At1g68620 (Arabidopsis thaliana)S09.A15-
At3g01690 (Arabidopsis thaliana)S09.A20-
At1g13610 (Arabidopsis thaliana)S09.A23-
At5g20520 (Arabidopsis thaliana)-type peptidaseS09.A24-
At5g38220 (Arabidopsis thaliana)S09.A25-
At5g14390 (Arabidopsis thaliana)-type peptidaseS09.A27-
At2g24320 (Arabidopsis thaliana)S09.A28-
At1g32190 (Arabidopsis thaliana)-type peptidaseS09.A30-
At3g30380 (Arabidopsis thaliana)S09.A32-
At4g31020 (Arabidopsis thaliana)-type peptidaseS09.A33-
At1g66900 (Arabidopsis thaliana)-type peptidaseS09.A34-
YqiA protein (Escherichi coli)S09.A40-
aes protein (acetyl esterase) (Escherichi coli)S09.A47Yes
PFC0950c g.p. (Plasmodium falciparum)S09.A66-
CG11935 protein (Drosophila melanogaster)S09.A67-
CG18642 (Drosophila melanogaster)S09.A68-
CG15111 protein (Drosophila melanogaster)S09.A69-
dpf-6 g.p. (Caenorhabditis elegans)S09.A77Yes
Y97E10AL.2 (Caenorhabditis elegans)S09.A78-
T07H6.1 g.p. (Caenorhabditis elegans)S09.A79-
F01D5.8 g.p. (Caenorhabditis elegans)S09.A80-
K04G2.2 g.p. (Caenorhabditis elegans)S09.A81-
dpf-4 g.p. (Caenorhabditis elegans)S09.A83-
F01D5.7 g.p. (Caenorhabditis elegans)S09.A84-
PFD0185c g.p. (Plasmodium falciparum)S09.A95-
DDB_G0281415 g.p. (Dictyostelium discoideum)S09.A96-
vegetative specific protein h5 (Dictyostelium discoideum)S09.A97-
BSU23640 g.p. (Bacillus subtilis)S09.B04-
PF3D7_0805000 g.p. (Plasmodium falciparum)S09.B05-
subfamily S9C non-peptidase homologuesnon-peptidase homologueYes
subfamily S9C unassigned peptidasesunassigned-
Subfamily S9D
Name Peptidase subfamily S9D
Subfamily type peptidase S09.021 - glutamyl endopeptidase C (Arabidopsis thaliana), MEROPS Accession MER0004925 (peptidase unit: 650-911)
Active site residues S780 D854 H888 
Statistics Sequences: 915
Identifiers: 1
Identifiers with PDB entries: 0
Other databases INTERPRO IPR001375
PANTHER PTHR11731
PFAM PF00326
PFAM PF07859
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
glutamyl endopeptidase CS09.021-
subfamily S9D non-peptidase homologuesnon-peptidase homologue-
subfamily S9D unassigned peptidasesunassigned-
Peptidases not assigned to subfamily
Peptidases and Homologues MEROPS ID Structure
bat5 peptidaseS09.022-
D230019K24Rik peptidase (Mus musculus)S09.023-
Mername-AA264 putative peptidase (LP_1002 protein) (Lactobacillus plantarum)S09.024Yes
lysophospholipase II (Homo sapiens)S09.025-
predicted hydrolase of the alpha/beta-hydrolase fold (Homo sapiens)S09.027-
AlbD protein (Pantoea dispersa)S09.031-
hypothetical proteinS09.062-
protein bat5S09.065-
Mername-AA240 putative peptidase (Mus musculus)S09.068-
puromycin hydrolaseS09.072Yes
highly similar to acyl-protein thioesterase 1 (Homo sapiens)S09.941Yes
esterase/lipase (Homo sapiens)S09.942Yes
acyl-CoA thioesterase 4 (Homo sapiens)S09.943Yes
acyl-coenzyme A thioesterase 6 (Homo sapiens)S09.944-
hypothetical esterase/lipase/thioesteraseS09.945-
esterase 6 (Drosophila melanogaster)S09.947-
para-nitrobenzyl esterase (Bacillus subtilis)S09.948Yes
cephalosporin C deacetylaseS09.949Yes
acyl-protein thioesterase 1 (Schizosaccharomyces pombe)S09.952-
carboxylesterase 6 (Rattus norvegicus)S09.953-
carboxylesterase homologue (Rattus norvegicus)S09.954-
carboxylesterase homologue (Rattus norvegicus)S09.955-
carboxylesterase homologue (Rattus norvegicus)S09.956-
carboxylesterase homologue (Rattus norvegicus)S09.957-
hypothetical protein flj40219S09.958-
hypothetical protein flj37464S09.959-
hypothetical protein flj33678S09.960-
2210023G05RIK proteinS09.961-
BC026374 protein (Mus musculus)S09.962-
liver carboxylesteraseS09.964-
carboxylesterase rl1 (Rattus norvegicus)S09.969-
putative carboxylesterase (Rattus norvegicus)S09.970-
carboxylesterase ES31 (Mus musculus)S09.971-
putative carboxylesterasecS09.972-
dipeptidylpeptidase homologue DPP6S09.973Yes
dipeptidylpeptidase homologue DPP10S09.974Yes
carboxylesterase homologue (Mus musculus)S09.975-
protein similar to Mus musculus chromosome 20 open reading frame 135S09.976-
kynurenine formamidaseS09.977-
thyroglobulin precursorS09.978-
acetylcholinesteraseS09.979Yes
cholinesteraseS09.980Yes
carboxylesterase D1S09.981-
liver carboxylesteraseS09.982-
carboxylesterase 2S09.984-
bile salt-dependent lipaseS09.985Yes
neuroligin 3S09.987-
neuroligin 4, X-linkedS09.988Yes
neuroligin 4, Y-linkedS09.989-
esterase DS09.990Yes
arylacetamide deacetylaseS09.991-
KIAA1363-like proteinS09.992-
hormone-sensitive lipaseS09.993-
neuroligin 1S09.994Yes
neuroligin 2S09.995-
liver carboxylesterase 1S09.996-
carboxylesterase 2S09.997-
9030624L02RIK-like proteinS09.998-
carboxylesteraseS09.999-
At3g27320 (Arabidopsis thaliana)-type peptidaseS09.A05-
At5g25770 (Arabidopsis thaliana)S09.A06-
At2g45600 (Arabidopsis thaliana)S09.A07-
At5g14310 (Arabidopsis thaliana)S09.A08-
At2g45610 (Arabidopsis thaliana)S09.A11-
At5g62180 (Arabidopsis thaliana)S09.A14-
At5g19630 (Arabidopsis thaliana)S09.A16-
At3g47590 (Arabidopsis thaliana)S09.A17-
At2g19550 (Arabidopsis thaliana)S09.A18-
At1g29840 (Arabidopsis thaliana)S09.A19-
At1g26120 (Arabidopsis thaliana)-type peptidaseS09.A21-
At5g15860 (Arabidopsis thaliana)-type peptidaseS09.A26-
At4g17150 (Arabidopsis thaliana)-type peptidaseS09.A29-
At3g47560 (Arabidopsis thaliana)S09.A31-
hypothetical ORF Ynl320wp (Saccharomyces cerevisiae)S09.A35-
YfhR protein (Escherichi coli)S09.A36-
YeiG protein (Escherichi coli)S09.A39-
YieL protein (Escherichi coli)S09.A41-
YpfH protein (Escherichi coli)S09.A43-
YjfP protein (Escherichi coli)S09.A46-
Gm438 protein (Mus musculus)S09.A48-
acyl-coenzyme A:N-acyltransferase 1S09.A49-
acyl-coenzyme A amino acid N-acyltransferase 2S09.A50-
acyl-coenzyme A thioesterase 5S09.A51-
acyl-coenzyme A thioesterase 2, mitochondrialS09.A52-
mCG4926 protein (Mus musculus)S09.A53-
mCG51558 protein (Mus musculus)S09.A54-
AT3G15650 protein (Arabidopsis thaliana)S09.A55-
AT5G20060 protein (Arabidopsis thaliana)S09.A56-
AT3G19970 protein (Arabidopsis thaliana)S09.A57-
MDB19.2 protein (Arabidopsis thaliana)S09.A59-
acyl-coenzyme A thioesterase 4S09.A60-
acyl-coenzyme A thioesterase 6S09.A61-
F16b3.4 protein (Arabidopsis thaliana)S09.A62-
AT14896 protein (Drosophila melanogaster)S09.A63-
CG7529 protein (Drosophila melanogaster)S09.A71-
CG9542 protein (Drosophila melanogaster)S09.A72Yes
Y43f8a.3 g.p. (Caenorhabditis elegans)S09.A82-
F27c8.6 g.p. (Caenorhabditis elegans)S09.A85-
F16F9.4 g.p. (Caenorhabditis elegans)S09.A86-
T28C12.4a g.p. (Caenorhabditis elegans)S09.A87-
T28C12.5 g.p. (Caenorhabditis elegans)S09.A88-
acetylcholinesterase (Caenorhabditis elegans)S09.A89-
ZC376.2 g.p. (Caenorhabditis elegans)S09.A90-
Y71G12A.4 g.p. (Caenorhabditis elegans)S09.A91-
YDL057W g.p. (Saccharomyces cerevisiae)S09.A98-
SPCC417.12 (Schizosaccharomyces pombe)S09.A99-
SPAPB1A11.02 g.p. (Schizosaccharomyces pombe)S09.B01-
DDB_G0288631 g.p. (Dictyostelium discoideum)S09.B03-
ytmA g.p. (Bacillus subtilis)S09.B06-
yjcH g.p. (Bacillus subtilis)S09.B07-
K05B2.4 g.p. (Caenorhabditis elegans)S09.B09-
C31H5.6 g.p. (Caenorhabditis elegans)S09.B10-
si:dkey-183c16.7 g.p. (Brachydanio rerio)S09.B11-
si:dkeyp-89c11.2 g.p. (Brachydanio rerio)S09.B12-
family S9 non-peptidase homologuesnon-peptidase homologueYes
family S9 unassigned peptidasesunassignedYes