Family S14

Family

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

Summary for family S14

NamePeptidase family S14 (ClpP endopeptidase family)
Family type peptidaseS14.001 - peptidase Clp (type 1) (Escherichia coli), MEROPS Accession MER0000474 (peptidase unit: 1-207)
Content of familyPeptidase family S14 contains endopeptidase Clp and its homologues.
History Identifier created: Biochem.J. 290:205-218 (1993)
Endopeptidase Clp is an oligomeric complex consisting of 20 or 26 subunits. There are just two types of subunit: an ATP-binding subunit (ClpA or ClpX in Escherischia coli) and a peptidase subunit (ClpP). The subunits form two different ring structures consisting of seven peptidase subunits and six ATP-binding subunits, respectively. The ring structures are stacked. The ATPase component acts as a molecular chaperone that can catalyze the unfolding of stable proteins if they possess an exposed site that can be recognized by the chaperones (Weber-Ban et al., 1999; Kim et al., 2000; Singh et al., 2000).
Catalytic typeSerine
Active site residuesS111 H136 D185 
Active siteThe catalytic triad has been determined to be in the order Ser, His, Asp. This is an arrangement not seen in peptidases of any other family.
Activities and specificitiesCleavage occurs preferentially following nonpolar residues (Arribas & Castano, 1993; Thompson & Maurizi, 1994), but cleavage has been observed after polar and even charged residues. Without the presence of an ATP-binding domain, ClpP can act only on oligopeptides.
InhibitorsInhibition by PMSF was reported by Halperin et al., 2001.
Molecular structureEach endopeptidase ClpP subunit consists of six repeats of an alpha/beta unit with a seventh unit protruding so that the shape resembles a hatchet, with the protruding unit being the handle (Rawlings & Barrett, 2004). There are two beta sheets which give the structure a beta/beta/alpha fold. Native ClpP exists as a homotetradecamer. There are two rings of seven subunits which form a cylinder with a central channel. The 21 active site residues are arranged around the interior channel, with the pores only allowing the entry of one helix or beta strand. ClpA and ClpX recognize and bind substrates by virtue of specific motifs located at either the N-terminus or C-terminus of the protein (Levchenko et al., 1997). When bound, the protein is unfolded from the end and translocated into the ClpP chamber (Ortega et al., 2000; Lee et al., 2001; Reid et al., 2001).
ClanSK
Basis of clan assignmentType family of clan SK.
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi -  
Plants details  
Animals details  
Viruses details  
Biological functionsClp peptidases have important roles in the both protein quality control and the regulatory degradation of specific proteins. The ClpXP and ClpAP complexes are responsible for the degradation of nascent polypeptides whose synthesis is interrupted by pauses in translation caused by damage to the mRNA or by deficiencies in the components required for translation. When a pause in translation occurs an 11 amino acid peptide (AADENYALAA), referred to as the SsrA-tag, is co-translationally added to the C-terminus of the growing chain (Keiler et al., 1996). The SsrA-tag is recognised by the ATP-binding components of the Clp complex, targeting the protein for degradation (Gottesman et al., 1998). A specificity-enhancing factor, SspB, has been identified that increases the rate of degradation of SsrA-tagged proteins (Levchenko et al., 2000). A role for ClpAP has also determined in the targeting of proteins with hydrophobic or basic amino acids at the N-terminus, which is rare in normal cell proteins (Tobias et al., 1991).
Statistics for family S14Sequences:12820
Identifiers:15
Identifiers with PDB entries:11
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Other databases CATH 3.90.226.10
INTERPRO IPR001907
PANTHER PTHR10381
PFAM PF00574
SCOP 52097
Peptidases and Homologues MEROPS ID Structure
peptidase Clp (type 1)S14.001Yes
peptidase Clp (type 2)S14.002Yes
peptidase Clp (type 3)S14.003Yes
peptidase Clp (type 5)S14.005-
peptidase Clp (type 6)S14.006Yes
peptidase Clp (type 7)S14.007-
ClpP1 peptidase (Streptomyces-type)S14.008Yes
ClpP2 peptidase (Streptomyces-type)S14.009-
ClpP4 peptidase (plant)S14.010Yes
PFC0310c peptidaseS14.011Yes
YmfB g.p. (Bacillus subtilis)S14.012-
At1g02560 (Arabidopsis thaliana)-type peptidaseS14.A01Yes
At5g23140 (Arabidopsis thaliana)-type peptidaseS14.A02Yes
At1g66670 (Arabidopsis thaliana)-type peptidaseS14.A03Yes
clpp-1 g.p. (Caenorhabditis elegans)S14.A04-
family S14 non-peptidase homologuesnon-peptidase homologueYes
family S14 unassigned peptidasesunassigned-