Family M96

Family

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

Summary for family M96

Family type peptidaseM96.001 - Tiki1 peptidase (Homo sapiens), MEROPS Accession MER0105341 (peptidase unit: 20-505)
Content of family
History Identifier created: MEROPS 9.9 (23 August 2013)
The Wnt signalling pathway is important during embryogenesis. Tiki1 is a transmembrane protein expressed in the dorsal Spemann-Mangold Organizer, which is a cluster of cells in the developing embryo of an amphibian that induces development of the central nervous system. Tiki1 antagonizes Wnt signalling by releasing an octopeptide from the N-terminus of a Wnt protein, which does not affect secretion of the Wnt protein, but does prevent it from binding its receptor (Zhang et al., 2012).
Catalytic typeMetallo
Active site residuesH60 E87 E161 R304 N305 H332 
Active siteInhibition by chelating agents have indicated that Tiki1 might be a metallopeptidase (Zhang et al., 2012). From its albeit distant sequence similarity to TraB proteins and erythromycin esterase, Tiki1 is assumed to be a cocatalytic zinc metallopeptidase, binding two ions of zinc per molecule. Zinc-binding residues have been predicted to be His60,Glu87, Arg304, Asn305, His332, and Glu161 to be a catalytic residue (Sanchez-Pulido & Ponting, 2013). If correct, this would be the first occurrence of an Asn being a metal ligand in a metallopeptidase, However, the metal ions in erythromycin esterase are thought to be non-catalytic and instead a His/Glu dyad is thought to be responsible for activating water (Morar et al., 2012).
Activities and specificitiesAn N-terminal octapeptide is removed from the Wnt-3a protein, with cleavage occurring at at Leu+Ala bond (Zhang et al., 2012).
InhibitorsZhang et al., 2012 have shown that Wnt-3a processing by Tiki1 is inhibited by the metal chelating agent 1,10-phenanthroline but not by bestatin.
Molecular structureTiki is a secreted protein with an N-terminal signal peptide and a C-terminal transmembrane region (Zhang et al., 2012). From the proposed relationship to erythromycin esterase, Tiki1 would possess a fold unlike that of any other metallopeptidase (Sanchez-Pulido & Ponting, 2013) and would be the representative of a new clan.
Clanunassigned
Distribution of family Bacteria details  
Archaea -  
Protozoa -  
Fungi details  
Plants -  
Animals details  
Viruses -  
Biological functionsTiki1 is required for development of the head during embryogenesis by interfering with the Wnt signalling pathway (Zhang et al., 2012).
Statistics for family M96Sequences:1059
Identifiers:2
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
Tiki1 peptidaseM96.001-
Tiki2 peptidaseM96.002-
family M96 non-peptidase homologuesnon-peptidase homologue-
family M96 unassigned peptidasesunassigned-