Family A28

Family

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

A28A

Summary Holotypes Alignment Tree Genomes Literature

A28B

Summary Holotypes Genomes Literature

Summary for family A28

Family type peptidaseA28.001 - DNA-damage inducible protein 1 (Saccharomyces cerevisiae), MEROPS Accession MER0030084 (peptidase unit: 210-324)
Content of family
History Identifier created: MEROPS 9.5 (1 July 2011)
Members of family A28 were predicted to be peptidases in 2001 (Krylov et al., 2001). Solution of the tertiary structure of DDI1 from Saccharomyces cervisiae confimed the structural similarity to pepsin (A01.001), and that the protein exists as a homodimer (Sirkis et al., 2006), as does retropepsin (A02.001). To date, proteolytic activity has been shown for skin SASPase (A28.004; Matsui et al., 2011,Bernard et al., 2005) and , and retropepsin inhibitors such as nelfinavir have been shown to bind (White et al., 2011). The activity of DNA-damage inducible protein 1 (A28.001) from Leishmania major against synthetic substrates of pepsin was inhibited by pepstatin and DANLME
Catalytic typeAspartic
Active siteAn aspartate (Asp220) is conserved which is presumed to be an active site residue and mutation of this residue abolishes the DNA repair role (Gabriely et al.,2008).
Activities and specificitiesSkin SASPasehas been shown to activate itself (Bernard et al., 2005) and to activate profilaggrin, which then induces cross-linking in keratin intermediate filaments (Matsui et al., 2011). Absense of active SASPase leads to dry skin with a yhicker than usual stratum corneum.
InhibitorsIn Leishmania major growth, proliferation and survival is affected by nelfinavir, which was shown to bind to DDI1, the only retropepsin-like protein in the Leishmania genome (White et al., 2011).
Molecular structureFrom the protein sequence, DDI1 from Saccharomyces cervisiae has been predicted to contain three domain: an N-terminal ubiquitin-like domain, a retropepsin-like domain, and a C-terminal ubiquitin-associated domain (Gabriely et al., 2008), The tertiary structure of of the retropepsin-like domain has been solved (Sirkis et al., 2006), confirming relationship to retropepsin, and consequently family A28 is included in clan AA.
ClanAA
Distribution of family Bacteria details  
Archaea details  
Protozoa details  
Fungi details  
Plants details  
Animals details  
Viruses -  
Biological functionsThe DDI1 ('DNA-damage inducible 1') gene is transcribed is conjunction with a the gene for 3-methyladenine DNA glycosylase, which encodes an enzyme that initiates a DNA base-excision-repair pathway (Liu & Xiao, 1997). The DDI1 protein has been shown to be important in cell cycle control, mediated via the N- and C-terminal domains (Gabriely et al., 2008). DDI1 is also important for the repression of protein secretion by Saccharomyces (White et al., 2011). Activation of profilaggrin by SASPase induces cross-linking in keratin intermediate filaments in the skin, and absense of active SASPase leads to dry skin with a thicker than usual stratum corneum (Matsui et al., 2011).
Pharmaceutical and biotech relevanceA possible target for antiparasite therapy, particularly Leishmania (White et al., 2011).
Statistics for family A28Sequences:2979
Identifiers:13
Identifiers with PDB entries:3
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Subfamily A28A
Name Peptidase subfamily A28A
Subfamily type peptidase A28.001 - DNA-damage inducible protein 1 (Saccharomyces cerevisiae), MEROPS Accession MER0030084 (peptidase unit: 210-324)
Active site residues D220 
Statistics Sequences: 1440
Identifiers: 10
Identifiers with PDB entries: 3
Other databases INTERPRO IPR001995
INTERPRO IPR018061
PANTHER PTHR12917
PFAM PF00077
PFAM PF09668
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
DNA-damage inducible protein 1A28.001Yes
nuclear receptor-interacting protein 3A28.002-
DNA-damage inducible protein 2A28.003Yes
gene name 1700011N24Rik (Mus musculus)A28.A01Yes
C01G5.6 (Caenorhabditis elegans)A28.A02-
At3g13235 (Arabidopsis thaliana)A28.A03-
DDB_G0288187 (Dictyostelium discoideum)A28.A04-
CG4420 g.p. (Drosophila melanogaster)A28.A05-
putative v-snare binding protein (Schizosaccharomyces pombe)A28.A06-
PF14_0090 (Plasmodium falciparum)A28.A07-
subfamily A28A non-peptidase homologuesnon-peptidase homologue-
subfamily A28A unassigned peptidasesunassigned-
Subfamily A28B
Name Peptidase subfamily A28B
Subfamily type peptidase A28.004 - skin SASPase (Mus musculus), MEROPS Accession MER0057496 (peptidase unit: 189-324)
Active site residues D210 
Statistics Sequences: 1539
Identifiers: 3
Identifiers with PDB entries: 0
Other databases INTERPRO IPR021109
PANTHER PTHR37006
PFAM PF00077
PFAM PF09668
PFAM PF13650
PFAM PF13975
Downloadable files Sequence library [FastA format]
Sequence alignment [FastA format]
Phylogenetic tree [Newick format]
Peptidases and Homologues MEROPS ID Structure
skin SASPaseA28.004-
DDB_G0279931 (Dictyostelium discoideum)A28.A08-
K02A2.6 (Caenorhabditis elegans)A28.A09-
subfamily A28B non-peptidase homologuesnon-peptidase homologue-
subfamily A28B unassigned peptidasesunassigned-