Family S68


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

Summary for family S68

Family type peptidaseS68.001 - PIDD auto-processing protein unit 1 (Homo sapiens), MEROPS Accession MER0020001 (peptidase unit: 421-454)
Content of familyPeptidase family S68 contains autolytic endopeptidases.
History Identifier created: MEROPS 7.7 (23 January 2007)
The 'PIDDosome' is a complex of three proteins - PIDD, RAIDD and procaspase-2 (C14.006) - which forms when damage to DNA occurs. The PIDDosome either activates NF-kappaB, leading to cell survival, or caspase-2, which leads to apoptosis.
Catalytic typeSerine
Active site residuesH444 S446 
Active siteThe catalytic mechanism is proposed to be similar to that of nucleoporin 145 (S59.001). 'Acyl-shift chemistry' is proposed to be the catalytic mechanism where the residue bearing the nucleophile is at the new C-terminus. A catalytic dyad is required and again in comparison with nucleoporin 145 the second member is proposed to be the histidine residue in the P3 position. It therefore follows that two active sites are present in the PIDD protein: His444 and Ser446; and His586 and Ser588. Mutational analysis has confirmed the importance these residues (Tinel et al., 2007).
Activities and specificitiesHuman PIDD protein (S68.001) autolyses at two SerTrp bonds. Cleavage at Ser446 releases fragments known as PIDD-N and PIDD-C. Further cleavage at Ser588 releases the fragment known as PIDD-CC.
Molecular structureThe PIDD protein has an N-terminal region containing seven leucine-rich repeats and a ZU-5 domain, and a C-terminal region containing a death domain and a ZU-5 domain. Following proteolysis, the fragments remain associated via the ZU-5 domains. The active site motifs, HisPheSer (see the Alignment), are identical to those of peptidases in family S59, implying a common catalytic mechanism.
Distribution of family Bacteria -  
Archaea -  
Protozoa -  
Fungi -  
Plants -  
Animals details  
Viruses -  
Biological functionsFollowing proteolysis, the PIDD C-terminal fragments translocate from the cytoplasm to the nucleus where they lead to activation of cell survival or apoptotic pathways. PIDD-C is required for activation of NF-kappaB. Production of PIDD-CC leads to caspase-2 activation.
Statistics for family S68Sequences:180
Identifiers with PDB entries:0
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Peptidases and Homologues MEROPS ID Structure
PIDD auto-processing protein unit 1S68.001-
PIDD auto-processing protein unit 2S68.002-
family S68 non-peptidase homologuesnon-peptidase homologue-
family S68 unassigned peptidasesunassigned-