Family S71

Family

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

Summary for family S71

Family type peptidaseS71.001 - MUC1 self-cleaving mucin (Homo sapiens), MEROPS Accession MER0074260 (peptidase unit: 1034-1151)
Content of familyPeptidase family S71 contains self-cleaving precursor proteins.
History Identifier created: MEROPS 8.2 (4 August 2008)
Mucin 1 is synthesized as a preproprotein, and after removal of the signal peptide is processed into a two-chain form, known as subunits alpha and beta. Cleavage occurs at a GlySer bond within an SEA module. Levitin et al. (2005) have shown that processing is by autolysis. Other mucins also contain SEA domains but autolysis is believed to occur only where the motif around the cleavage site (Gly-Ser-Val/Ile-Val/Leu-Val) is conserved.
Catalytic typeSerine
Active site residuesS1098 
Active siteSite-directed mutagenesis has been used to identify the active site Ser, which is at the N-terminus of the beta chain. Substitution of this residue with Cys or Thr permitted processing (Levitin et al., 2005). The mucin precursor is only partially folded, and following cleavage it adopts a completely folded conformation. The Gly-Ser bond is under considerable strain in the precursor because of the partially folded conformation, and mutagenesis has shown that cleavage can occur, albeit slowly, even if the catalytic residue is replaced (Johansson et al., 2008). The catalytic mechanism has been suggested to be by an N --> O-acyl rearrangement at the cleavage site followed by hydrolytic resolution of the unstable ester and concomitant cleavage (Levitin et al., 2005), which is supported by studies with slow-cleaving mutants (Johansson et al., 2009).
Activities and specificitiesThe only known activity of this peptidase is the autolytic cleavage.
Molecular structureMucin 1 is a type I transmembrane protein, and processing occurs in the extracellular portion. The tertiary structure of processed SEA domain from human mucin 1 has been solved by nuclear magnetic resonance, showing a four strand beta sheet with four helices. Cleavage occurs between strands 2 and 3 (Macao et al., 2006).
Clanunassigned
Distribution of family Bacteria -  
Archaea -  
Protozoa -  
Fungi -  
Plants -  
Animals details  
Viruses -  
Biological functions
Statistics for family S71Sequences:692
Identifiers:2
Identifiers with PDB entries:1
Downloadable files Sequence library (FastA format)
Sequence alignment (FastA format)
Phylogenetic tree (Newick format)
Peptidases and Homologues MEROPS ID Structure
MUC1 self-cleaving mucinS71.001Yes
MUC3 self-cleaving mucinS71.002-
family S71 non-peptidase homologuesnon-peptidase homologue-
family S71 unassigned peptidasesunassigned-