Family S79

Family

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

Summary for family S79

Family type peptidaseS79.001 - CARD8 self-cleaving protein (Homo sapiens), MEROPS Accession MER0246409 (peptidase unit: 1-431)
Content of familyFamily S79 contains self-processing proteins.
History Identifier created: MEROPS 9.6 (29 February 2012)
The proteins CARD8 ('caspase activation and recruitment domain 8', S79.001) and NLRP1 ('nucleotide-binding domain leucine-rich repeat protein 1', S79.002) are components of the inflammosome, the multiprotein complex that activates caspase-1 (C14.001). Both CARD8 and NLRP1 undergo autolytic cleavage at a conserved Ser-Phe+Ser motif (D"Osualdo et al., 2011).
Catalytic typeSerine
Active site residuesS297 
Active sitein CARD8, the N-terminal serine following autoactivation (Ser297) has been shown to be essential for activity by mutagenesis, and is presumed to be the nucleophile. His252 and Glu285 have also been shown to be essential for cleavage by mutagenesis, but they are predicted to form a salt bridge and might have more to do with protein stability rather than being part of a catalytic triad; His270 and Glu279 are also required for autoprocessing (D"Osualdo et al., 2011). In NLRP1, Ser1213 and His1186 have been shown by mutagenesis to be important for processing (Finger et al., 2012). The catalytic mechanism in family S79 may be different to that of the PIDD protein (family S68, XS68-001), which is thought to have a similar structure, because the residue occupying P2 in PIDD (His) is replaced by Leu in NLRP1, which would be unable to form the ester intermediate during the N-O acyl rearrangement (Finger et al., 2012).
Activities and specificitiesThe only known proteolytic activity is autoactivation.
Molecular structureNo tertiary structure has been solved for any member of this family. Cleavage occurs within a domain known as FIIND (''Function to Find Domain') and modelling studies have suggested that the FIIND domain is structurally similar to the ZU5-UPA of the PIDD protein (D"Osualdo et al., 2011). It is therefore likely that families S68 and S79 will be members of the same as yet unidentified clan.
Clanunassigned
Distribution of family Bacteria -  
Archaea -  
Protozoa -  
Fungi -  
Plants -  
Animals details  
Viruses -  
Biological functionsNLRP1 has been shown to be associated with a number of human diseases including vitiligo (loss of skin pigmentation), rheumatoid arthritis and Crohns disease (Finger et al., 2012). Autoprocessing is prevented by a single nucleotide polymorphism near His1186 and a naturally occurring mRNA splice variant lacking exon 14, which in turn prevents NLRP1 being activated.
Statistics for family S79Sequences:542
Identifiers:7
Identifiers with PDB entries:2
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Peptidases and Homologues MEROPS ID Structure
CARD8 self-cleaving proteinS79.001Yes
NLRP1 self-cleaving proteinS79.002-
NLR family, pyrin domain containing 1B isoform 3 (Mus musculus)S79.A01-
NLR family, pyrin domain containing 1A (Mus musculus)S79.A02-
NACHT, leucine rich repeat and PYD containing 1, partial, peptidase unit 1 (604-926) (Mus musculus)S79.A03-
NACHT, leucine rich repeat and PYD containing 1, partial, peptidase unit 1 (1946-2301) (Mus musculus)S79.A04-
NLR family, pyrin domain containing protein 1C (Mus musculus)S79.A05-
family S79 non-peptidase homologuesnon-peptidase homologue-
family S79 unassigned peptidasesunassignedYes